Endothelial cells line blood vessels and lymph vessels, and remain in a quiescent state until inflammatory cues in underlying tissues cause them to become activated. Endothelial cell activation consists of changes in morphology, as well as gene expression. Activated endothelial cells promote vascular/lymphatic vessel fluid leakage and the extravasation of leukocytes from the lumen of blood and lymph vessels to adjoining tissues. The extravasation of leukocytes from the lumen of blood and lymph vessels into an adjoining tissue is induced by the expression of leukocyte adhesion molecules in activated endothelial cells that line lymph and blood vessels. The expression of leukocyte adhesion molecules in these activated endothelial cells promotes the rolling of leukocytes in the blood or lymph vessel, firm adhesion of leukocytes within the blood or lymph vessel, and finally, extravasation of leukocytes out of the blood or lymph vessels and into the adjoining tissue.
Increased extravasation of leukocytes and blood/lymph vessel fluid leakage plays a role in inflammation, inflammatory disorders, and vessel (blood and lymph vessel) fluid leakage disorders. For example, increases in endothelial cell adhesion molecule expression and leukocyte extravasation are associated with several inflammatory disorders, including cardiovascular disease and atherosclerosis. Conversely, loss of endothelial cell adhesion molecules can cause one to be immune-compromised, thus illustrating the important role for endothelial cells in the promotion of inflammation, and the maintenance of vascular and lymphatic homeostasis.
Models of inflammation in murine animal models are well documented. Mice lacking the leukocyte adhesion molecules intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E- or P-selectin (or combinations thereof) display reduced levels of acute inflammation. Furthermore, mice lacking apolipoprotein E (ApoE) or low-density lipoprotein (LDL) receptors, which are prone to atherosclerosis, display reduced atherosclerosis when these leukocyte adhesion molecules are absent.